Favorable Clinical Outcome in Cholangiocellular Carcinoma is Associated with the CC Genotype in the GNB3 825 C>T SNP – a Putative Novel Independent Prognostic Marker

Background/Aims: Cholangiocellular carcinoma (CCA) has a devastating prognosis. While markers enabling a precise prediction of the clinical outcome have long remained scarce, certain single-nucleotide polymorphisms (SNPs) in genes that modulate G protein-signal transduction and apoptosis were recently identified as potential predictive parameters. We here aimed at extending the panel of SNPs suitable for predicting the outcome of CCA. Methodology: Forty Caucasian patients with CCA (and a control collective of 40 age- and sex-matched healthy white Caucasians) were genotyped to simultaneously elucidate putative associations between clinical outcome and the following SNP genotypes: G protein β3 (GNB3) 825 C>T; B﷓cell lymphoma-2 (Bcl-2) –938 C>A; and myeloid-cell leukemia-1 (Mcl-1) –386 C>G. Results: Patients homozygous for the C allele of the GNB3 825 C>T polymorphism exhibited a significantly prolonged overall survival compared with patients displaying the CT or TT genotypes (median survival [months]: 31 vs. 13 vs. 7; p<0.05) and also showed lower bilirubin serum levels. In addition, the CC genotype of the BCL2–938 C>A polymorphism was associated with higher GLDH serum levels [U/l] of 29.8±7.1 vs. 17.7±4.3 vs. 5.6±1.7 when comparing CC vs. CA vs. AA (p<0.05). Conclusions: In the GNB3 825 C>T SNP–a putative novel independent prognostic marker for CCA–the CC genotype is associated with a favorable clinical outcome. Further prospective studies are needed to confirm these results and to reveal additional functional SNP effects.

Cholangiocellular carcinoma SNPs prognostic value